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REVIEW ARTICLE

A comprehensive review of drug-resistant epilepsy and animal models: Existing and emerging therapies and future research directions

Aman Shrivastava1* ,  Jeetendra Kumar Gupta2 ,  Sumeet Dwivedi3 ,  Amit Anand4 ,  Darshana Sharma5 ,  Sonam Upadhyay6 ,  Prerna Chaturvedi7
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1 Department of Pharmacology, College of Pharmacy, Institute of Professional Studies, Gwalior, Madhya Pradesh, India
2 Department of Pharmacology, Institute of Pharmaceutical Research, GLA University, Mathura, Uttar Pradesh, India
3 Department of Pharmacognosy, Acropolis Institute of Pharmaceutical Education and Research, Indore, Madhya Pradesh, India
4 Department of Pharmacognosy, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Mysuru, Karnataka, India
5 Department of Pharmaceutical Chemistry, Acropolis Institute of Pharmaceutical Education and Research, Indore, Madhya Pradesh, India
6 Department of Pharmaceutics, Jai Narain College of Pharmacy, JNCT Professional University, Bhopal, Madhya Pradesh, India
7 Department of Pharmaceutical Chemistry, Chameli Devi Institute of Pharmacy, Indore, Madhya Pradesh, India
Advanced Neurology, 025210062 https://doi.org/10.36922/AN025210062
Received: 21 May 2025 | Revised: 2 July 2025 | Accepted: 22 July 2025 | Published online: 14 August 2025
(This article belongs to the Special Issue Advances in the pathogenesis, diagnosis and treatment of epilepsy)
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Epilepsy is a long-term neurological disorder that results in recurring, uncontrolled seizures. These kinds of seizures are caused by excessively high and irregular electrical discharge in the central nervous system. Epilepsy is among the most common neurological disorders, with approximately 50–70 new cases/100,000 people every year. This review critically examines the current landscape of pharmacological experimental animal models employed in the study of drug-resistant and refractory epilepsy, shedding light on the complexities of this multifaceted disorder. Through an extensive analysis of preclinical models, the review explores the diverse mechanisms underlying resistance to antiepileptic drugs, emphasizing the need for innovative therapeutic strategies. This review was conducted using a comprehensive search of databases, including PubMed, Scopus, and Web of Science, focusing on studies published from 2000 to 2024. Articles were selected based on relevance to drug-resistant epilepsy (DRE) models, emerging technologies, and translational potential, using keywords such as DRE, animal models, and epileptogenesis. In addition, emerging experimental approaches, such as optogenetics, chemogenetics, and advanced imaging techniques, were scrutinized. Furthermore, this review outlines innovative approaches, including novel pharmacotherapies, gene therapies, and precision medicine interventions, that hold promise for overcoming drug resistance. By synthesizing current knowledge and identifying gaps, this article aims to guide future research directions and stimulate innovative strategies for developing effective interventions for drug-resistant and refractory epilepsy. Ultimately, a comprehensive grasp of experimental models and innovative approaches is crucial for advancing our understanding of epilepsy pathophysiology and paving the way for more efficacious and personalized therapeutic interventions.

Keywords
Epilepsy
Clinical implication
Pharmacological mechanism
Experimental therapeutic strategies
Pharmacotherapy
Drug-resistant epilepsy
Funding
None.
Conflict of interest
The authors declare that they have no competing interests.
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Advanced Neurology, Electronic ISSN: 2810-9619 Print ISSN: 3060-8589, Published by AccScience Publishing
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